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Metformin and oncogenic pathways: Crosstalk between energy sensing and tumor progression

Ying Zhang1, Long Zhao1, Kai Zhang1

  • 1Department of Pharmacy, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, 157000, China.

Molecular and Cellular Probes
|February 13, 2026
PubMed

Insights

Metformin, a diabetes drug, shows potential as an anti-cancer agent by activating AMP-activated protein kinase (AMPK) to inhibit tumor growth. Further research is needed to clarify its complex effects in cancer prevention and treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Metabolic Diseases

Background:

  • Metformin is a first-line oral biguanide medication for type 2 diabetes mellitus.
  • Preclinical and epidemiological data suggest metformin possesses anti-cancer properties.
  • Its anti-tumor effects are mediated through both insulin-dependent and insulin-independent pathways.

Purpose of the Study:

  • To review the multifaceted mechanisms of metformin's anti-cancer activity.
  • To discuss the potential of metformin in cancer prevention and treatment.
  • To highlight the challenges and complexities observed in clinical studies.

Main Methods:

  • Review of preclinical studies on metformin's anti-tumor effects.
  • Analysis of epidemiological data linking metformin use to cancer outcomes.
  • Examination of clinical trial results regarding metformin's efficacy in cancer.
  • Focus on molecular mechanisms including AMPK activation and mTOR inhibition.

Main Results:

  • Metformin activates AMP-activated protein kinase (AMPK), inhibiting the mTOR pathway, leading to cell cycle arrest and apoptosis.
  • It modulates key oncogenic signaling pathways (PI3K/Akt, Erk) and influences tumor metabolism, angiogenesis, and immunity.
  • Inhibition of mitochondrial complex I by metformin disrupts cancer cell bioenergetics and the Warburg effect.
  • Clinical studies present mixed results, indicating a complex therapeutic profile.

Conclusions:

  • Metformin exhibits diverse anti-cancer mechanisms, impacting tumor growth, metabolism, and signaling.
  • While promising, its clinical application in cancer therapy requires further rigorous investigation due to complex and sometimes conflicting results.
  • Metformin's potential in cancer prevention and treatment warrants continued research to optimize its use.
Keywords:
AMPK/mTOR signalingCancer metabolismMetforminTumor progression

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